Sagone A L, Husney R M, O'Dorisio M S, Metz E N
Blood. 1984 Jan;63(1):96-104.
We have reported previously that human granulocytes have an irreversible fall in their endogenous reduced soluble sulfhydryls following zymosan stimulation. In the present study, we demonstrate that stimulated granulocytes release one or more reactive oxygen species (ROS) with the capacity to oxidize reduced glutathione (GSH). One or more of these compounds is stable enough to be detected in the supernatant. The formation of these stable oxidants appears to require H2O2 and heme or a heme-containing enzyme. However, once formed, the compound reacts with GSH without these factors. The ROS is not superoxide or hydroxyl radical, since neither superoxide dismutase nor the hydroxyl scavengers, mannitol and benzoic acid, change the rate of the reaction. Methionine has recently been demonstrated to be oxidized to a sulfoxide by a reactive oxygen species that is dependent on H2O2 and heme for its production. We found that methionine could directly react with the same ROS that degrades GSH. The ROS also has the capacity to oxidize iodide and fix halogen to proteins. Our data indicate that stimulated granulocytes release a ROS with the capacity to oxidize GSH, react with methionine, and oxidize and fix I- to protein. The compound, therefore, appears dependent on H2O2 and the myeloperoxidase system for its production, and is either hypochlorous acid (HOCI) or a compound derived from HOCI, such as a chloramine. The capacity of GSH to react with this ROS suggests an additional role for this tripeptide in cellular protection against oxidant injury.
我们之前报道过，酵母聚糖刺激后人类粒细胞内源性还原型可溶性巯基会发生不可逆下降。在本研究中，我们证明受刺激的粒细胞会释放一种或多种具有氧化还原型谷胱甘肽（GSH）能力的活性氧（ROS）。这些化合物中的一种或多种足够稳定，可在上清液中检测到。这些稳定氧化剂的形成似乎需要过氧化氢（H₂O₂）和血红素或含血红素的酶。然而，一旦形成，该化合物在没有这些因素的情况下也能与GSH反应。ROS不是超氧化物或羟基自由基，因为超氧化物歧化酶以及羟基清除剂甘露醇和苯甲酸都不会改变反应速率。最近已证明甲硫氨酸会被一种依赖H₂O₂和血红素产生的活性氧氧化为亚砜。我们发现甲硫氨酸能直接与降解GSH的同一种ROS反应。该ROS还具有氧化碘离子并将卤素固定到蛋白质上的能力。我们的数据表明，受刺激的粒细胞释放出一种具有氧化GSH、与甲硫氨酸反应以及将碘离子氧化并固定到蛋白质上能力的ROS。因此，该化合物的产生似乎依赖于H₂O₂和髓过氧化物酶系统，并且要么是次氯酸（HClO），要么是源自HClO的化合物，如氯胺。GSH与这种ROS反应的能力表明这种三肽在细胞抵御氧化损伤方面具有额外作用。
